Immune Reactivity of a 20-mer Peptide Representing the Zika E Glycan Loop Involves the Antigenic Determinants E-152/156/158.

Etienne Frumence,Bénédicte Vanwalscappel,Wildriss Viranaicken,Jessica Andries,Philippe Desprès,Jason Decotter,Juliano G Haddad,Gilles Gadea

doi:10.3390/v12111258

Abstract

Mosquito-borne Zika virus (ZIKV) causes a severe congenital syndrome and neurological disorders in humans. With the aim to develop a live-attenuated ZIKV strain, we generated a chimeric viral clone ZIKALIVax with African MR766-NIID strain as backbone and the envelope E protein of epidemic Brazilian BeH810915 strain. The MR766-NIID residues E-T152/I156/Y158 were introduced into BeH810915 E protein leading to a nonglycosylated ZIKALIVax. Recently, we reported that the residues E-152/156/158 that are part of ZIKV glycan loop (GL) region might have an impact on the availability of neutralizing antibody epitopes on ZIKV surface. In the present study, we evaluated the antigenic reactivity of a synthetic 20-mer peptide representing the ZIKALIVax GL region. The GL-related peptide was effective for the detection of GL-reactive antibody in mouse anti-ZIKALIVax immune serum. We showed that the residue E-158 influences the antigenic reactivity of GL-related peptide. The ZIKALIVax peptide was effective in generating mouse antibodies with reactivity against a recombinant E domain I that encompasses the GL region. The GL peptide-reactive antibodies revealed that antigenic reactivity of E-domain I may be impacted by both residues E-152 and E-156. In conclusion, we proposed a role for the residues E-152/156/158 as key antigenic determinants of ZIKV glycan loop region.

Highlights

Mosquito-borne Zika virus (ZIKV) belonging to flavivirus genus of Flaviviridae family is the etiologic agent of Zika congenital syndrome and neurological disorders in humans [1,2,3,4,5]
These results showed that glycan loop (GL) peptide-reactive antibody has ability to recognize the GL region into a reconstituted envelope domains: Domain I (EDI) of ZIKALIVax regardless of the presence of a glycan to recognize the GL region into a reconstituted EDI of ZIKALIVax regardless of the presence of a linked to N154
It has been recently reported that glycan loop of Asian-genotype ZIKV encompasses a highly conserved linear epitope, with His residue at position E-158 playing a key role in the antibody binding [34]

Summary

Introduction

Mosquito-borne ZIKV belonging to flavivirus genus of Flaviviridae family is the etiologic agent of Zika congenital syndrome and neurological disorders in humans [1,2,3,4,5]. ZIKV strains are mostly clustered into African and Asian lineages [6,7]. There has been unexpected expansion of the geographic distribution of ZIKV strains of Asian lineage and their rapid spread caused major epidemics in the South Pacific in 2013 and South America including Brazil in 2015 [2,7,8]. Vaccination has been proposed as an efficient strategy to prevent ZIKV infection in humans [9,10,11]. It is well established that elicitation of a protective antibody response is a critical step in the development of safe and efficient Zika vaccines [12,13,14,15].

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